One-pot synthesis of dibenzo[b,h][1,6]naphthyridines from 2-acetylaminobenzaldehyde: application to a fluorescent DNA-binding compound

Abstract

Dibenzo[b,h][1,6]naphthyridines were synthesized in one pot by reacting 2-acetylaminobenzaldehyde with methyl ketones under basic conditions via four sequential condensation reactions. This method was also applied to the synthesis of 1,2-dihydroquinolines. 6-Methyl-1,6-dibenzonaphthyridinium triflates showed strong fluorescence, and the fluorescence intensities were changed upon intercalation into double-stranded DNA.

Synthesis of 1,6‐Naphthyridine and Its Derivatives: A Systematic Review

“…Okuma and co-workers (2014) established a new synthetic route for the preparation of dibenzo[b,h] [1,6]naphthyridines (222) in one-pot synthesis by reacting 2-acetylaminobenzalde-hyde with methyl ketones under basic conditions (Scheme 57). [73] In the past, dibenzo[b,h] [1,6]naphthyridines were synthesized in two steps. [48] This Okuma et al method provides the best alternative for the synthesis of dibenzo[b,h] [1,6] naphthyridines in a one-pot operation.…”

“…The formation of desired products takes place via a sequence of reactions, namely condensation, hydrolysis, imination, aza-Morita-Baylis Hillman cyclization, hydrolysis, oxidation, and intramolecular condensation (Figure 16). [73] The presence of 1 mol equivalent of (20 M) sodium hydroxide under refluxing condition, 2-acetylaminobenzaldehyde, and methyl ketones gave polymeric products. While intermittent addition of the excess amount of sodium hydroxide (2 eq.…”

Merging Visible‐Light Photoredox and Lewis Acid Catalysis for the Intramolecular Aza‐Diels–Alder Reaction: Synthesis of Substituted Chromeno[4,3‐b]quinolines and [1,6]Naphthyridines

“…Substituted chromenoquinolines and 5,6‐dihydrodibenzo[ b , h ][1,6]naphthyridines are biologically significant compounds, which widely occur in natural products, pharmaceuticals, and bioactive materials . For examples, 6 H ‐chromeno[4,3‐ b ]quinolines have been used as estrogen receptor β‐selective ligands and as bioimaging reagents, the spiro analogues of benzothiazolylchromeno derivatives have shown cytotoxic activity against breast cancer cells, and dibenzo[ b , h ][1,6]naphthyridines have found applications in fluorescent DNA labelling due to their fluorescent properties . Because of their biological importance, the development of methods for the preparation of them has attracted much attention from organic chemists .…”

“…For examples, 6 H ‐chromeno[4,3‐ b ]quinolines have been used as estrogen receptor β‐selective ligands and as bioimaging reagents, the spiro analogues of benzothiazolylchromeno derivatives have shown cytotoxic activity against breast cancer cells, and dibenzo[ b , h ][1,6]naphthyridines have found applications in fluorescent DNA labelling due to their fluorescent properties . Because of their biological importance, the development of methods for the preparation of them has attracted much attention from organic chemists . One of the most efficient methods for their preparation was the aza‐Diels–Alder reaction of N ‐aryl imines derived from aldehydes and anilines with electron‐rich olefins or alkynes .…”

Synthesis and Fluorescence Properties of 1,1‐Dimethyl‐1,4‐Dihydrodibenzo[b,h][1,6]naphthyridinium Iodides: Turn‐on Type Detection of DNA

“…A cascade reaction in which a reactive intermediate from one step directly undergoes further transformations is very important in organic synthesis, because such sequential processes not only rapidly build up complex molecules but also efficiently enhance the chemo‐ and regioselectivity of the overall transformation . We reported the synthesis of 6‐methyl‐1,6‐dibenzonaphthyridinium triflates 1 through a cascade approach . These compounds produce fluorescence at 420 nm upon irradiation at 360 nm, and they have the ability to intercalate into DNA.…”