Synlett 2013; 24(15): 1945-1948
DOI: 10.1055/s-0033-1339467
letter
© Georg Thieme Verlag Stuttgart · New York

A Two-Step Synthesis of Selected 1,2,3,4-Tetrahydroquinoxaline Derivatives from N-Aryl-2-nitrosoanilines and Arylidenecyanoacetic Esters

Magdalena Królikiewicz
a  The Faculty of Chemistry, University of Warsaw, Pasteura 1, 02-093 Warsaw, Poland
,
Kacper Błaziak
b  Institute of Organic Chemistry, Polish Academy of Sciences, Kasprzaka 44, 01-224 Warsaw 42, Poland   Fax: +48(22)6326681   eMail: [email protected]
,
Witold Danikiewicz
b  Institute of Organic Chemistry, Polish Academy of Sciences, Kasprzaka 44, 01-224 Warsaw 42, Poland   Fax: +48(22)6326681   eMail: [email protected]
,
Zbigniew Wróbel*
b  Institute of Organic Chemistry, Polish Academy of Sciences, Kasprzaka 44, 01-224 Warsaw 42, Poland   Fax: +48(22)6326681   eMail: [email protected]
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Publikationsverlauf

Received: 10. Juni 2013

Accepted after revision: 21. Juni 2013

Publikationsdatum:
09. August 2013 (online)


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

 
  • References and Notes

    • 1a For a review of recent advances in the synthesis of quinoxalines and medicinal compounds containing a quinoxaline moiety, see: Mamedov VA, Zhukova NA. Prog. Heterocycl. Chem. 2012; 24: 55
    • 1b Eary CT, Jones ZS, Groneberg RD, Burgess LE, Mareska DA, Drew MD, Blake JF, Laird ER, Balachari D, O’Sullivan M, Allen A, Marsh V. Bioorg. Med. Chem. Lett. 2007; 17: 2608
    • 1c Ohtake Y, Naito A, Hasegawa H, Kawano K, Morizono D, Taniguchi M, Tanaka Y, Matsukawa H, Naito K, Oguma T, Ezure Y, Tsuriya Y. Bioorg. Med. Chem. 1999; 7: 1247
    • 1d Torisu K, Kobayashi K, Iwahashi M, Nakai Y, Onoda T, Sugimoto I, Okada Y, Matsumoto R, Nanbu F, Ohuchida S, Nakai H, Toda M. Bioorg. Med. Chem. 2004; 12: 5361
    • 1e Sikorski JA. J. Med. Chem. 2006; 49: 1
    • 1f Jacobsen EJ, Stelzer LS, Belonga KL, Carter DB, Im WB, Sethy VH, Tang AH, VonVoigtlander PF, Petke JD. J. Med. Chem. 1996; 39: 3820
    • 1g Barrows TH, Farina PR, Chrzanowski RL, Benkovic PA, Benkovic SJ. J. Am. Chem. Soc. 1976; 98: 3678
    • 2a Wohl A, Aue W. Ber. Dtsch. Chem. Ges. 1901; 34: 2442
    • 2b Wohl A. Ber. Dtsch. Chem. Ges. 1903; 36: 4135
    • 2c Serebryanyi SB. Ukrain. Khim. Zhur. 1955; 21: 350
    • 3a Wróbel Z, Kwast A. Synlett 2007; 1525
    • 3b Wróbel Z, Kwast A. Synthesis 2010; 3865
  • 4 Kwast A, Stachowska K, Trawczyński A, Wróbel Z. Tetrahedron Lett. 2011; 6484
  • 5 Wróbel Z, Stachowska K, Grudzień K, Kwast A. Synlett 2011; 1439
  • 6 Wróbel Z, Stachowska K, Kwast A, Gościk A, Królikiewicz M, Pawłowski R, Turska I. Helv. Chim. Acta 2013; 96: 956
  • 7 Wróbel Z, Królikiewicz M. J. Heterocycl. Chem. 2013; 50: in press
  • 8 Królikiewicz M, Cmoch P, Wróbel Z. Synlett 2013; 24: 973
  • 9 Instability of similar hydroxylamines was reported: López-Cantarero J, Cid MB, Poulsen TB, Bella M, Ruano JL. G, Jørgensen KA. J. Org Chem. 2007; 72: 7062
  • 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.
  • 12 Comesse S, Sanselme M, Daich A. J. Org. Chem. 2007; 73: 5566