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Synlett 2013; 24(15): 1945-1948
DOI: 10.1055/s-0033-1339467
DOI: 10.1055/s-0033-1339467
letter
A Two-Step Synthesis of Selected 1,2,3,4-Tetrahydroquinoxaline Derivatives from N-Aryl-2-nitrosoanilines and Arylidenecyanoacetic Esters
Weitere Informationen
Publikationsverlauf
Received: 10. Juni 2013
Accepted after revision: 21. Juni 2013
Publikationsdatum:
09. August 2013 (online)
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Abstract
Reaction of N-aryl-2-nitrosoanilines with alkyl arylidenecyanoacetates in the presence of Et3N in MeCN leads to substituted 1,2,3,4-tetrahydroquinoxaline derivatives in reasonable yields. The reaction comprises nucleophilic addition of the nitrosoaniline to the Michael acceptor followed by cyclization involving the nitroso group. Since the reactive nitrogen groups in N-aryl-2-nitrosoanilines are of opposite character the reaction is regioselective and additionally it was found to be diastereoselective.
Supporting Information
- for this article is available online at http://www.thieme-connect.com/ejournals/toc/synlett.
- Supporting Information
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References and Notes
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- 10 General Procedure for the Synthesis of Compound 4 To a solution of N-aryl-2-nitrosoaniline 1 (1 mmol) and arylidenecyanoacetic ester 2 (1.2 mmol) in dry MeCN (10 mL) was added Et3N (0.73 mL, 5 mmol). The mixture was stirred until the reaction was complete (TLC control, times shown in Table 1). The mixture was then evaporated to dryness, treated with AcOH (10 mL), then Zn dust (650 mg, 10 mmol) was added. The mixture was stirred for 30 min at r.t. and evaporated to dryness in vacuo. The residue was treated with EtOAc (30 mL) and aq NaHCO3, filtered through a Celite pad, and extracted with EtOAc (3 × 20 mL). The extract was dried (Na2SO4), the solvent was evaporated, and the product was isolated by column chromatography (SiO2, hexane–EtOAc).
- 11 Analytical Data for Representative Products Compound 3a: grey crystals; mp 132–134 °C (Et2O–hexane). 1H NMR (500 MHz, DMSO-d 6): δ = 0.95 (t, J = 7.0 Hz, 3 H), 2.20 (s, 3 H), 4.00–4.06 (m, 2 H), 5.60 (s, 1 H), 6.10 (s, 1 H), 6.84 (dd, J = 8.5, 1.1 Hz, 1 H), 7.10 (s, 5 H), 7.45 (d, J = 8.5 Hz, 1 H), 7.22–7.28 (m, 3 H), 7.33–7.40 (m, 2 H), 10.52 (s, 1 H). 13C NMR (125 MHz, DMSO-d 6): δ = 13.4, 20.5, 63.0, 66.2, 70.9, 113.2, 114.2, 117.6, 118.5, 126.6, 128.1, 128.8, 129.1, 129.2, 130.2, 132.9, 133.9, 136.4, 137.4, 139.6, 162.8. Anal. Calcd for C25H22ClN3O3: C, 67.04; H, 4.95; N, 9.38. Found: C, 67.08; H, 5.03; N, 9.28. Compound 4a: white crystals; mp 185–187 °C (EtOH). 1H NMR (500 MHz, DMSO-d 6): δ = 1.01 (t, J = 7.0 Hz, 3 H), 2.24 (s, 3 H), 4.06–4.17 (m, 2 H), 5.25 (s, 1 H), 6.27 (d, J = 2.3 Hz, 1 H), 6.74 (dd, J = 8.5, 2.3 Hz, 1 H), 6.81 (d, J = 8.5 Hz, 1 H), 6.89–6.92 (m, 2 H), 7.11–7.15 (m, 2 H), 7.32 (s, 5 H), 7.76 (s, 1 H). 13C NMR (125 MHz, DMSO-d 6): δ = 14.1, 20.9, 60.2, 63.7, 64.8, 114.2, 116.2, 116.4, 119.5, 123.1, 126.3, 128.7, 128.9, 129.2, 130.6, 130.8, 133.6, 135.8, 136.9, 142.1, 165.4. MS (EI): m/z = 433 (36), 432 (29), 431 (100), 406 (13), 405 (10), 404 (35), 360 (28), 359 (23), 358 (81), 333 (21), 332 (18), 331 (58), 330 (13), 329 (30), 328 (12), 327 (54). Anal. Calcd for C25H22ClN3O2: C, 69.52; H, 5.13; N, 9.73. Found: C, 69.60; H, 5.19; N, 9.79.
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