Efficient synthesis of 4-substituted-ortho-phthalaldehyde analogues: toward the emergence of new building blocks (Beilstein Journal of Organic Chemistry)

Abstract 4-Methoxy-ortho-phthalaldehyde and 4-hydroxy-ortho-phthalaldehyde are potentially useful molecules for fluorimetric analysis of a variety of amines and for the elaboration of complex molecular architectures. Nevertheless, literature generally describes their synthesis in very low yield (below 5%), mainly due to the inefficiency of the last oxidation step. In this paper, we report a reliable synthesis of 4-substituted-ortho-phthalaldehyde analogues in 51% overall yield owing to the addition of a protecting step of the unstable key intermediate 4,5-dihydroisobenzofuran-5-ol. Oxidation and deprotection steps were also studied in order to provide an effective availability of these two dialdehyde compounds that may increase their future applications. Beilstein J. Org. Chem. 2019, 15, 721–726. doi:10.3762/bjoc.15.67