One-Pot Regioselective Synthesis of 2,5,6,7-Tetrahydroimidazo [1,2-a]imidazol-3-ones Starting from (Vinylimino)phosphoranes

Abstract

A new, one-pot, regioselective preparation of 2,5,6,7-tetrahydroimidazo[1,2-a]imidazol-3-ones by a sequential aza-Wittig/nucleophilic addition/cyclization reaction was developed. The aza-Wittig reactions of ethyl (2Z)-3-aryl-2-[(triphenylphosphoranylidene)amino] acrylates with aryl isocyanates produced carbodiimide intermediates that were then treated sequentially with 2-aminoethanol and tosyl chloride/triethylamine to give the corresponding (2Z)-2-[(substituted)benzylidene]-2,5,6,7-tetrahydro-3H-imidazo[1,2-a]imidazol-3-ones in good overall yields and with high regioselectivity.

Key words

imidazoimidazolone - aza-Wittig reaction - nucleophilic addition - regioselectivity

• References and Notes

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• 22 (2Z)-2-Benzylidene-7-(4-tolyl)-2,5,6,7-tetrahydro-3H-imidazo[1,2-a]imidazol-3-one (6ab); Typical Procedure (Vinylimino)phosphorane 1a (2.26 g, 5 mmol) was treated with 4-tolyl isocyanate (2b; 0.67 g, 5 mmol) in CH₂Cl₂ (15 mL) at r.t. for 4 h to give carbodiimide 3ab (monitored by TLC), which was used directly in the next step. Ph₃P=O was extracted from the mixture with 1:2 Et₂O–PE (20 mL), and carbodiimide 3ab was treated with 2-aminoethanol (4; 0.60 mL, 5 mmol) in CH₂Cl₂ (15 mL) with stirring for 4 h. The mixture was then concentrated and the residue was dissolved in MeCN (25 mL). Et₃N (2.8 mL, 20 mmol) was added, followed after 30 min by TosCl (1.05 g, 5.5 mmol). The mixture was then stirred at r.t. for about 6 h until 5ab was completely consumed (TLC). The reaction was quenched with sat. aq NH₄Cl, and the mixture was extracted with CH₂Cl₂. The extracts were dried (Na₂SO₄) and the crude mixture was purified directly by flash column chromatography [silica gel PE–CH₂Cl₂ (4:1 to 2:1)] to give a light-yellow solid; yield: 1.24 g (82%); mp 196­–198 °C.IR: 2954, 2924, 2854, 1730, 1659, 1603, 1591, 1565, 1519, 1492, 1459, 1376, 1305 cm^–1. ¹H NMR (600 MHz, CDCl₃): δ = 8.09 (d, J = 7.6 Hz, 2 H), 7.64 (d, J = 8.4 Hz, 2 H), 7.41 (t, J = 7.6 Hz, 2 H), 7.31 (t, J = 7.3 Hz, 1 H), 7.27–7.23 (m, 2 H), 6.76 (s, 1 H), 4.40–4.31 (m, 2 H), 4.00–3.90 (m, 2 H), 2.36 (s, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 166.3, 158.7, 145.2, 135.9, 135.0, 133.2, 130.9, 129.8, 128.5, 128.4, 119.0, 117.1, 50.7, 36.7, 20.8. HRMS (ESI): m/z [M + H]⁺ calcd for C₁₉H₁₈N₃O: 304.1450; found: 304.1444.