Intermolecular Reductive Heterocyclization of Potassium 2-Acyl-1,1,3,3-tetracyanopropenides

Abstract

2-Acyl-1,1,3,3-tetracyanopropenides undergo intermolecular reductive heterocyclization under the action of mercaptoethanol or sodium borohydride, resulting in the formation of 2-[5-amino-4-cyano-2-alkyl(aryl)furan-3(2H]-ylidene)malononitriles in high yields and excellent purities, These are of interest as potential precursors to organic nonlinear optical (NLO) materials and prospective antibiofilm antimicrobial agents.

Key words

furans - heterocycles - nucleophilic addition - reduction - ring closure

• References and Notes

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• 20 Figure 2 shows the atom numbering in 3a. Displacement ellipsoids are drawn at the 50% probability levels. Cell parameters (3a): a = 13.9259(5), b = 8.8709(4), c = 10.5576(6) Å, β = 90°, β = 98.44(0)°, γ = 90°; V = 1290.12(10) ų, Z = 4, D _calc = 1.278 g cm^–3. The crystal is monoclinic and the space group is P1 21/c1. CCDC 912663 for 3a contains the supplementary crystallographic data for this Letter. These data can be obtained free of charge from the Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
• 21 Typical Procedure for the Preparation of 2-[5-Amino-2-aryl-4-cyanofuran-3(2H)-ylidene]malononitriles 3a–j via the Reaction of Propenides 1 with Sodium Borohydride NaBH₄ (0.56 g, 15 mmol) was added to a solution of potassium 2-acyl-1,1,3,3-tetracyanopropenide 1 (10 mmol) in H₂O (20 mL), and the mixture was stirred at r.t. until the reaction became colorless. The resulting solution was filtered and then neutralized by addition of aq 5% H₂SO₄. The white precipitate was filtered, recrystallized from AcOH, and dried in vacuo. Compound 3a: yield 82% (2.03 g; via reaction with mercaptoethanol) or 86% (2.13 g; via reaction with NaBH₄), white solid, mp 262–263 °С (dec.). ¹H NMR (500.13 MHz, DMSO-d ₆): δ = 6.81 (1 H, s, CH), 7.41–7.52 (5 H, m, Ph), 10.07 (2 H, s, NH₂). IR (mineral oil): 3318, 3115 (NH₂), 2223, 2212 (CN), 1663 (C=C) cm^–1. MS (EI, 70 eV): m/z (%) = 248 [M]⁺ (53), 221 [M – HCN]⁺ (7), 205 [M – HNCO]⁺ (33), 178 [M – HNCO – HCN]⁺ (100). 2-[5-Amino-4-cyano-2-methylfuran-3(2H)-ylidene]malononitrile (3k) NaBH₄ (0.56 g, 15 mmol) was added to a solution of potassium 2-acetyl-1,1,3,3-tetracyanopropenide 1 (10 mmol) in H₂O (20 mL), and the mixture was stirred at r.t. until the reaction became colorless. The resulting solution was filtered, then neutralized by addition of aq 5% H₂SO₄ and subsequently extracted with EtOAc (3 × 10 mL). The combined organic layers were dried (CaCl₂), filtered, and concentrated in vacuo. The resulting residue was purified by flash chromatography (SiO₂, EtOAc), and the relevant fractions were concentrated in vacuo until a precipitate formed. The white solid was filtered, washed with hexane (3 × 5 mL) and dried in air; yield 62% (1.15 g), mp 208–210 °С (dec.). ¹H NMR (500.13 MHz, DMSO-d ₆): δ = 1.56 (3 H, d, ³ J = 6.6 Hz, СН₃), 5.84 (1 H, q, ³ J = 6.7 Hz, CH), 9.98 (2 H, br s, NH₂). IR (mineral oil): 3366, 3254 (NH₂), 2229, 2214 (CN), 1684 (C=C) cm^–1. MS (EI, 70 eV): m/z (%) = 186 [M]⁺ (22), 159 [M – HCN]⁺ (100), 116 [M – HNCO – HCN]⁺ (47). Typical Procedure for the Preparation of 2-[5-Amino-2-aryl-4-cyanofuran-3(2H)-ylidene]malononitriles 3a–h via the Reaction of Propenides 1 with Mercaptoethanol Mercaptoethanol (1.95 g, 25 mmol) was added dropwise to a solution of potassium 2-acyl-1,1,3,3-tetracyanopropenide 1 (10 mmol) in H₂O (20 mL), and the mixture was stirred at r.t. for 10–15 min. The white precipitate was filtered, recrystallized from AcOH, and dried in vacuo. 2-[5-Amino-4-cyano-2-(2′-hydroxyethylthio)-2-methylfuran-3(2H)-ylidene]malononitrile (4a) Mercaptoethanol (1.17 g, 15 mmol) was added dropwise to a solution of potassium 2-acetyl-1,1,3,3-tetracyanopropenide 1 (10 mmol) in H₂O (20 mL), and the mixture was stirred at r.t. for 10 min. The yellow precipitate was filtered, recrystallized from i-PrOH (10 mL), and dried in air; yield 72% (1.89 g), mp 205–207 °С (dec.). ¹H NMR (500.13 MHz, DMSO-d ₆): δ = 1.94 (3 H, s, CH₃), 3.79 (3 H, s, CH₃O), 2.52–2.58 (1 Н, m, SCH₂), 2.60–2.67 (1 Н, m, SCH₂), 3.51 (2 H, br s, ОCH₂), 4.98 (1 H, br s, OH), 10.12 (2 H, br s, NH₂). IR (mineral oil): 3620 (OH), 3368, 3254 (NH₂), 2224, 2209 (CN), 1696 (C=C) cm^–1. MS (EI, 70 eV): m/z (%) = 262 [М]⁺ (7), 185 (31), 184 (10), 78 (23), 60 [C₂H₄S]⁺ (44), 59 (30), 47 (67), 43 (77). Anal. Calcd for C₁₁H₁₀N₄O₂S: C, 50.37; H, 3.84; N, 21.36. Found: C, 50.68; H, 3.82; N, 21.71
• 22 Typical Procedure for the Preparation of 2-[5-Amino-2-aryl-4-cyano-2-(2′-hydroxyethylthio]furan-3(2H)-ylidene)malononitriles 4b–f Mercaptoethanol (1.17 g, 15 mmol) was added dropwise to a solution of potassium 2-acyl-1,1,3,3-tetracyanopropenide 1 (10 mmol) in a mixture of EtOH (20 mL) and Et₃N (1.0 g, 10 mmol). The resulting mixture was stirred at r.t. until reaction was complete (TLC, 20–25 min), filtered, and the filtrate poured into distilled H₂O (40 mL) and subsequently neutralized by addition of aq 5% H₂SO₄. The white precipitate was filtered, recrystallized from i-PrOH (10 mL), and dried in air. Compound 4b: yield 86% (2.79 g), mp 137–139 °С (dec.). ¹H NMR (500.13 MHz, DMSO-d ₆): δ = 2.65–2.70 (1 H, m, SCH₂), 2.73–2.79 (1 H, m, SCH₂), 3.61 (2 H, t, ³ J = 6.4 Hz, ОCH₂), 4.98 (1 Н, br s, ОН), 7.50–7.53 (3 H, m, Ar), 7.56–7.58 (2 H, m, Ar), 10.27 (2 H, br s, NH₂). IR (mineral oil): 3634 (OH), 3391, 3218 (NH₂), 2230, 2210 (CN), 1673 (C=C) cm^–1. MS (EI, 70 eV): m/z (%) = 324 [М]⁺ (1), 248 (12), 178 (17), 92 (23), 77 (41), 60 [C₂H₄S]⁺ (100), 59 (27)