An Efficient and Facile Synthesis of Iminoquinazolinedione Derivatives by Solid-State Diels–Alder Reaction under Catalyst-Free Conditions

Abstract

A solvent- and catalyst-free Diels–Alder reaction with 6-(2-morpholinovinyl)-1,3-dimethyluracil, cinnamaldehyde, and an amine has been developed for the construction of iminoquinazoline-2,4-dione derivatives within a short reaction time. The method is clean, simple, and operation friendly.

Keywords

atom economy - solid-state Diels–Alder reaction - ­iminoquinazoline-2,4-dione - green alternative

• References and Notes

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• 16 General Procedure for the Syntheses of 4a–k A mixture of 6-(2-morpholinovinyl)-1,3-dimethyluracil (1a, 1 mmol), cinnamaldehyde (2, 1 mmol), and p-phenetidine (3a, 1 mmol) was finely ground, and the mixture was heated at 90 °C for 4 h. After the reaction was complete (TLC) the crude product mixture was dissolved in CHCl₃ and purified by column chromatography, eluting with hexane–EtOAc (1.5:1) to obtain pure 6-[(4-ethoxyphenylimino)methyl]-1,3-dimethyl-5-phenylquinazoline-2,4-dione (4a). Spectroscopic Data for Selected Compounds Compound 4a: brown solid; mp 188–190 °C. ¹H NMR (300 MHz, CDCl₃): δ = 8.64–8.61 (d, J = 9.0 Hz, 1 H, CH=CH), 8.01 (s, 1 H, CH=N), 7.39–7.36 (d, J = 9.0 Hz, 1 H, CH=CH), 7.44–6.80 (m, 9 H, H_arom), 4.04–4.00 (q, J = 3.6 Hz, 2 H, OCH₂), 3.71 (s, 3 H, NCH₃), 3.34 (s, 3 H, NCH₃), 1.40–1.38 (t, J = 3.54 Hz, 3 H, CH₃). ¹³C NMR (75 MHz, CDCl₃): δ = 160.8, 157.7, 155.2, 151.0, 145.9, 144.3, 142.9, 138.2, 132.7, 131.0, 128.4, 128.0, 127.5, 122.3, 116.4, 114.9, 113.8, 113.1 63.6, 31.5, 28.7, 15.0. IR (CHCl₃): 2979.1, 2927.2, 1708.1, 1662.8, 1603.0, 1505.3 cm^–1. MS (GC–MS): m/z = 413 [M]⁺. Anal. Calcd for C₂₅H₂₃N₃O₃: C, 72.62; H, 5.61; N, 10.16; O, 11.61. Found: C, 72.61; H, 5.55; N, 10.07; O, 11.54. Compound 4j: brown solid; mp 166–168 °C. ¹H NMR (300 MHz, CDCl₃): δ = 9.53 (s, 1 H, CH=N), 8.30–8.28 (d, J = 6.0 Hz, 1 H, CH=CH), 7.42–7.40 (d, J = 6.0 Hz, 1 H, CH=CH), 7.49–7.23 (m, 5 H, H_arom), 3.71 (s, 3 H, NCH₃), 3.34 (s, 3 H, NCH₃), 1.25 [s, 9 H, C(CH₃)₃]. ¹³C NMR (75 MHz, CDCl₃): δ = 190.4, 160.3, 150.8, 149.2, 145.1, 136.2, 132.8, 130.3, 128.5, 127.9, 114.0, 113.0, 31.7, 29.7, 29.3. IR (CHCl₃): 2923.9, 2853.9, 1712.0, 1663.6, 1594.0, 1571.8, 1476.7 cm^–1. MS (GC–MS): m/z = 349 [M]⁺. Anal. Calcd for C₂₁H₂₃N₃O₂: C, 72.18; H, 6.63; N, 12.03; O, 9.16. Found: C, 72.10; H, 6.61; N, 12.00; O, 9.09.