1-Hydroxy-2-aryl(alkyl)-1H-naphto[2,3-d]imidasole-4,9-diones, their alkylation and tautomerism

Nitrogen-containing polycyclic quinoid compounds are of interest because some of them have various types of biological activity including antitumor activity. Particular attention is drawn to quinoid N-oxides, which are potential oxidizers and sources of nitric oxide. It is known that 1-R-4,9-dioxo-1Н-naphtho[2,3-d]imidazole-4,9-diones and their oximation products, 1-R-4,9-dioxo-1Н-naphtho[2,3-d][1,2,3]triazol-2-oxid-4-оximes, exhibit antitumor activity comparable with that of doxorubicin. In this regard, it is of interest to study other naphthoquinone derivatives that contain the N-oxide fragment. We have improved the method for the synthesis of 1-hydroxy-2-phenyl-1H-naphtho[2,3-d]imidazole-4,9-dione and increased its yield from 67% to 84%. Two-dimensional NMR spectroscopy has been used to refine the spectral parameters of phenyl-1H-naphtho[2,3-d]imidazole-4,9-dione. It has been shown that alkylation of this compound leads to the formation of 11-methoxy(ethoxy)-2-phenyl-1H-naphtho[2,3-d]imidazole-4,9-dione. We have analyzed the 1Н and 13С NMR spectra of the synthesized alkylation products and electron absorption spectra of the studied initial compounds. Using the Gaussian-09 quantum chemical method DFT B3LYP/6-311++G(d,p), we have confirmed that 1-hydroxy-2-phenyl-1H-naphtho[2,3-d]imidazole-4,9-dione and 1-hydroxy-2-metyl-1H-naphtho[2,3-d]-imidazole-4,9-dione exists in two tautomeric forms, with the N-oxide form prevailing in dichloroethane.