A Short Preparation of Pyrroloquinoxalinones via a Cascade Reaction of N-Aryl-5-alkylamino-2-nitrosoanilines with Methyl 2-Cyanoalkanoates: Unexpected Direction of Nucleophilic Substitution of Hydrogen

Abstract

N-Aryl-2-nitrosoanilines possessing 5-alkylamino groups undergo a bisheteroannulation reaction with anions of 2-cyanoalkanecarboxylates resulting in pyrroloquinoxalinone derivatives. The cascade reaction involves condensation of the cyanoester anions with the nitroso group, unusual nucleophilic substitution of hydrogen in the nitrosoaniline-derived intermediate with the second carbanion molecule, and double intramolecular acylation of the amino functions.

Key words

carbanions - condensation - heterocycles - annulation - nucleophilic aromatic substitution

• References and Notes

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• 6 Wróbel Z, Stachowska K, Kwast A, Gościk A, Królikiewicz M, Pawłowski R, Turska I. Helv. Chim. Acta 2013; DOI: 10.1002/hlca.201200304.
• 7 Królikiewicz M, Wróbel Z. J. Heterocycl. Chem. 2013; in press
• 8 Analytical Data for Representative New Products Compound 3e: yellow crystals; mp 246 °C (dec.; hexane–EtOAc). ¹H NMR (400 MHz, CDCl₃): δ = 1.24 (s, 9 H), 2.54 (s, 3 H), 4.15 (s, 1 H), 5.77 (d, J = 2.1 Hz, 1 H), 6.59 (dd, J = 9.2, 2.1 Hz, 1 H), 7.26-7.29 (m, 2 H), 7.58–7.61 (m, 2 H), 8.17 (d, J = 9.2 Hz, 1 H). ¹³C NMR (100 MHz, CDCl₃): δ = 11.7, 29.4, 51.4, 97.7, 112.3, 121.5, 122.6, 130.1, 130.5, 134.6, 134.8, 135.4, 135.9, 149.5, 157.2. ESI-MS: m/z = 380 [M + Na]⁺, 358 [M + H]⁺. ESI-HRMS: m/z calcd for C₁₉H₂₁N₃O₂ ³⁵Cl [M + H]⁺: 358.1322; found: 358.1234. Compound 4a: white crystals; mp 179–180 °C (hexane–EtOAc). IR (KBr): 2236 (CN), 1755, 1672, 1621 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 1.17 (t, J = 7.4 Hz, 3 H), 1.35 (t, J = 7.4 Hz, 3 H), 2.38–2.45 (m, 2 H), 2.46 (s, 3 H), 2.96 (q, J = 7.4 Hz, 2 H), 3.64 (s, 3 H), 3.78 (s, 3 H), 6.11 (s, 1 H), 7.14–7.18 (m, 1 H), 7.38–7.43 (m, 1 H), 7.92 (s, 1 H). ¹³C NMR (100 MHz, CDCl₃): δ = 9.7, 10.8, 21.3, 27.1, 28.5, 50.0, 54.5, 56.0, 97.7, 118.1, 120.6, 126.9, 127.7, 127.8, 128.6, 130.9, 131.0, 132.9, 135.8, 139.7, 154.8, 156.9, 160.4, 168.7. MS (EI): m/z 420 (16), 419 (57), 390 (10), 361 (27), 360 (100), 333 (12). HRMS (EI): m/z calcd for C₂₄H₂₅N₃O₄: 419.1845; found: 419.1841. Compound 6b: yellow crystals; mp 148–151 °C (hexane–EtOAc). IR (KBr): 2241 (CN), 1731, 1670, 1627 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 0.95 (t, J = 7.4 Hz, 3 H), 1.36 (t, J = 7.4 Hz, 3 H), 1.51 (s, 9 H), 2.18–2.30 (m, 2 H), 2.93–3.02 (m, 2 H), 6.51 (s, 1 H), 7.25–7.29 (m, 2 H), 7.61–7.65 (m, 2 H), 7.85 (s, 1 H). ¹³C NMR (100 MHz, CDCl₃): δ = 8.0, 10.5, 27.0, 28.7, 31.6, 47.2, 59.3, 99.9, 117.0, 121.6, 124.9, 128.3, 129.5, 129.6, 130.6, 130.7, 134.2, 135.0, 135.8, 144.1, 154.4, 160.9, 170.9. MS (EI): m/z (%) = 450 (16), 449 (17), 448 (34), 395 (15), 394 (47), 393 (40), 392 (100), 365 (17), 364 (19), 363 (27), 337 (21), 336 (20), 335 (43). HRMS (EI): m/z calcd for C₂₅H₂₅N₄O₂Cl: 448.1666; found: 448.1687.

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• 12 General Procedure for the Synthesis of Pyrrolo-quinoxalinones 6a–j 5-Amino-N-aryl-2-nitrosoaniline (0.5 mmol) and methyl 2-cyanoalkanoate (1.1 mmol) were dissolved in dry MeCN (5 mL). DBU (0.4 mL, 2.68 mmol) was added in one portion, and the mixture was stirred at r.t. for the time specified in Table 2. The mixture was poured into sat. NH₄Cl (10 mL) and H₂O (10 mL), extracted with EtOAc (3 × 20 mL), dried with Na₂SO₄, and the crude product was chromatographed.
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