4-(N-Phthalimido)phenyl Isonitrile as a Novel Convertible Isocyanide Analogue with the Odorless Property as an Extra Bonus

Abstract

We explored a new isonitrile, namely 4-(N-phthalimido)phenyl isonitrile, with extraordinary features. The novel isocyanide has a pharmacophore, the phthalimido (Pht) group, that possesses promising pharmaceutical activities. We found that the novel isonitrile is unexpectedly odorless as an extra bonus which makes its handling easy in organic synthesis to serve as a scaffold for building several new amide derivatives through multicomponent reactions, overcoming the stink of common aromatic isonitriles such as phenyl isonitrile, benzyl isonitrile, p-nitrophenyl isonitrile, and ethyl 4-isocyano benzoate. The novel isonitrile 9 serves as a source of N-protected isonitrile with a Pht group, where the Pht group can be easily removed via hydrazinolysis, affording the corresponding primary amine/alcohol scaffold which could be used as a precursor to synthesize Passerini products via acylation directly to afford Passerini adducts 14 and 15 without carrying out the traditional Passerini three-component reaction; this new isonitrile is considered as a novel convertible isocyanide analogue.