Abstract
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.
Highlights
Inorganic acid halides react with disubstituted amides to form active complexes, halomethyleniminium salts, called Vilsmeier-Haack reagents [1] initially used to introduce formyl groups into activated aromatic and heteroatom compounds [2], and it knows several uses in chlorination [3], chloroformylation [4], aromatization [5], cyclization [6,7], ... etc
We propose the retrosynthesis showed below (Scheme1)
We tried to extend our study on acetophenone derivatives since thiophenes prepared from cyclones give a positive biological activity. In this communication we report that the conditions described above led to the formylation of thiophene instead of cyclisation confirmed by the NMR spectrum (1H δ = 9.55 ppm) and the presence of 2CH3 δ = 3.22 ppm shown in (Figure 2)
Summary
Inorganic acid halides react with disubstituted amides to form active complexes, halomethyleniminium salts, called Vilsmeier-Haack reagents [1] initially used to introduce formyl groups into activated aromatic and heteroatom compounds [2], and it knows several uses in chlorination [3], chloroformylation [4], aromatization [5], cyclization [6,7], ... etc. Thieno[2,3-d]pyrimidin-4(3H)-one is a common building block for drugs with diverse pharmaceutical activities [11]. It has been widely used for the preparation of new antibacterial [8], antitumor agents [12], and as central nervous system agents [13]. Our laboratory since its opening interested in the development and functionalization of heterocyclic compounds [13,14,15,16,17] as a part of our research, we try to introduce Vilmeier-Haack reaction in the synthesis of new Thieno[2,3-d]pyrimidin-4(3H)-one derivatives (Figure 1) combining the easiness and efficiency. Proc. 2020, 1, Firstpage-Lastpage; doi: FOR PEER REVIEW www.mdpi.com/journal/chemproc
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