Synthesis of benzo[ f]quinazoline-1,3(2 H,4 H)-diones

Abstract

We report the synthesis of polycyclic uracil derivatives. The method is based on palladium-catalysed Sonogashira-Hagihara and Suzuki-Miyaura cross-coupling reactions followed by Brønsted acid-mediated cycloisomerisation. The developed methodology tolerates various functional groups and leads to moderate up to quantitative yields of the final products. The impact of different functional groups on the optical properties was studied by UV-vis and fluorescence spectroscopy.

Keywords: cross-coupling; cyclization; heterocycles; palladium.

Figure 1

Synthesis of uracil-based alkynes and aryl structures [,–65].

Figure 2

Structures of uracil derivatives A, B, and C.

Scheme 1

Strategy for the synthesis of the cyclised product 5. Conditions: i) Br₂ (2 equiv), Ac₂O (1.5 equiv), AcOH, 25 °C, 1 h [65]; ii) Pd(PPh₃)Cl₂ (5 mol %), CuI (5 mol %), NEt₃ (10 equiv), DMSO, 25 °C, 6 h; iii) Pd(PPh₃)₄ (10 mol %), NaOH (3 equiv), 1,4-dioxane/water 5:1, 100 °C, 1 h; iv) p-TsOH (20 equiv), toluene, 100 °C, 4 h.

Scheme 2

Synthesis and isolated yields of 1,3-dimethyl-5-aryl-6-[2-(aryl)ethynyl]uracils 4a–i. Reaction conditions: 3 (1 equiv), boronic acid (1.2 equiv), Pd(PPh₃)₄ (5 mol %), NaOH (3 equiv), 1,4-dioxane/water 5:1, 100 °C, 1 h.

Scheme 3

Scope and isolated yields of the synthesis of 5. Reaction conditions: 4 (1 equiv), p-TsOH·H₂O (20 equiv), toluene, 100 °C, 4 h.

Scheme 4

Proposed reaction mechanism of the cyclisation with N,N-dimethylanilino functional groups.

Figure 3

UV–vis absorption (left) and emission (right, λ_ex = 400 nm) spectra of 5a, 5d, 5f, 5g, 5h, and 5i in dichloromethane (c = 1⋅10⁻⁵ M).